(ATP III), which advise physicians to aim for an LDL level of less than 100 mg/dL for patients with established

coronary artery disease or a 10-year risk for a cardiac event of 20% or higher based on Framingham criteria,

and to consider an "optional" target of 70 mg/dL for the same patient group. (See chart.) American Heart
Association guidelines, similarly, call 70 mg/dL a "reasonable" goal for very high-risk patients.

Dr. Paul S. Jellinger, lead author of the guidelines, said that aiming for an
LDL below 70 mg/dL for all patients with CAD, or those with diabetes plus at
least one additional risk factor, reflects both a mounting scientific consensus
and current practice. For patients at high risk – including people with diabetes
and those with two or more risk factors and a 10-year Framingham risk of
coronary heart disease – the AACE recommends an LDL target of less than 100
mg/dl.

Though the Food and Drug Administration recently changed statin labeling to
reflect a slight hyperglycemia risk associated with their use, the new AACE
guideline reinforces that patients with diabetes should be treated
"aggressively."

Dr. Jellinger of the Center for Diabetes and Endocrine Care in Hollywood,
Fla., and professor of clinical medicine at the University of Miami also noted
that, the guideline also recommends that clinicians check the apolipoprotein B
levels of patients on LDL-lowering treatments. ApoB is a biomarker that
indicates LDL particle number and, indirectly, particle size. "Measuring apoB is
the easiest, cheapest, and most consistent way to tell us that we've reduced the
total number of LDL particles. It is more difficult to lower apoB than to lower
LDL."

While non-HDL is also a key measurement, and should be included in all
reports, Dr. Jellinger said, "We look at non-HDL as a very good way to start and
apoB as a very good final measurement to ascertain that you have reached your
pharmacotherapy goal."

The AACE guidelines advise physicians to look at apoB even when LDL levels
appear to be well controlled and at goal and consider apoB as a secondary
therapeutic target. Recommended apoB levels for patients at risk of CAD,
including those with diabetes, are less than 90 mg/dL, and less than 80 mg/dL
for patients with established CAD or diabetes and one or more additional risk
factors. The guidelines note the evidence here is not as strong as for the other
recommendations.

Measurements of homocysteine, uric acid, and plasminogen activator
inhibitor-1 are not routinely recommended by the AACE for use in stratifying
risk due to the uncertain evidence of benefit achieved by lowering these
factors. But the AACE encourages looking at the inflammatory markers highly
sensitive C-reactive protein (hsCRP) and in some patients lipoprotein-associated
phospholipase A2 (Lp-PLA2), when risk is uncertain and additional information is
needed to decide how aggressively to treat.

The guidelines note that while hsCRP can be useful in stratifying patients
with intermediate risk, this marker can be elevated by systemic inflammation and
obesity. Lp-PLA2, an enzyme found in arterial plaque, is more specific for
vascular sources of inflammation. "With both hsCRP and Lp-PLA2 elevated, it may
be appropriate to be more aggressive with treatment in a patient otherwise
considered at intermediate risk," Dr. Jellinger said.

Also helpful in cases requiring precise risk stratification are two
noninvasive measures of atherosclerosis: carotid intima media thickness and
coronary artery calcification (CAC). But since there is no definite evidence
that CAC, while strongly correlated with coronary atherosclerosis, independently
predicts coronary events, the guidance warns that these are not helpful when
performed routinely as a screening measure, which Dr. Jellinger said they often
are. Rather, "they should only be used in certain situations as adjuncts to
standard CVD risk factors to refine the patients' risk when considering more
aggressive therapy," he said.

The new guidelines recommend raising HDL-C levels as much as possible for
patients at risk of CAD, but minimallyto greater than 40 mg/dL in both men and
women.

While statins remain the cornerstone of therapy, determining the roles
fibrates and niacin should play in lowering triglycerides and raising HDL, and
in which patients, is more complicated.

Several scientific studies cited in the AACE guidelines support a clinical
benefit for the use of fibrates in patients whose triglycerides are greater than
200 and whose HDL is less than 40 mg/dL or 35 mg/dL for primary and secondary
prevention of cardiovascular events. There remains uncertain clinical benefit in
patients treated with fibrates for lesser triglyceride and HDL
abnormalities.

Niacin is also recommended for increasing HDL and reducing LDL-C and
triglycerides in certain patients despite results from AIM-HIGH, a randomized
controlled trial that was terminated early after it became clear that patients
whose LDL levels were very well controlled with simvastatin were seen not to
benefit from the addition of niacin.

Dr. Jellinger said that niacin may benefit patients with less well controlled
LDL and that the AACE is awaiting the results of another, larger niacin trial
(HPS2-THRIVE). "You probably don't have to start niacin if your LDL is very low.
When your LDL is higher, we don't yet know. It may be suitable," he said.

The guidelines also give more latitude as to when to order lipid testing.
More frequent lipid testing may be indicated in the following circumstances:
deterioration of diabetes control, the use of a new drug known to affect lipid
levels, atherothrombotic disease progression, considerable weight gain,
development of a new CAD risk factor and convincing new clinical trial evidence
suggesting stricter lipid goals. The AACE's position "ought to give comfort to
physicians who want to order more frequent lipid profiles under certain
circumstances," Dr. Jellinger said.